PROJECT SUMMARY Hepatitis C (HCV) viral infection is common among chronic dialysis patients in the United States (US) and associated with elevated risks of death and morbidity. Infection rates vary widely across dialysis units, with estimates ranging from 2 ? 14%. HCV infection increases the death rate among dialysis patients by 1.6 ? 2.4 fold. Kidney transplantation offers substantial improvements in survival and quality of life compared to dialysis, even in high risk subgroups such as the elderly and patients with diabetes. Unfortunately, the US transplant registry does not record HCV serostatus among wait-listed patients. Studies of kidney transplant outcomes for HCV+ patients have therefore been limited by single center populations, short follow-up, exclusive focus on post-transplant outcomes, and concerns about generalizability to the wider HCV+ population. It is unknown if there is a survival benefit of kidney transplant over dialysis for HCV+ patients, and if receipt of an HCV+ donor kidney affects this benefit. The landscape of HCV in dialysis and kidney transplantation has been greatly altered by the approval of direct acting antiviral agents (DAAs); however the ideal timing of DAA-based HCV therapy and its effects on transplant outcomes have not been determined. The optimal transplant strategy for HCV+ kidney transplant candidates remains unknown. Compared to uninfected kidney transplant candidates, HCV+ candidates have additional risk factors for removal from the waiting list, including progression of their liver disease, and a higher burden of comorbidities, including diabetes and cardiovascular disease (CVD), which can affect access to kidney transplant and mortality. Transplantation may reduce CVD risk, but may worsen other health conditions such as glycemic control. Also, HCV+ candidates have the unique option of accepting kidneys from HCV+ donors, a practice that carries risks of viral complications such as liver injury. The benefits of accepting a HCV+ organ, versus waiting for a HCV- negative kidney, may only be realized by individuals with deteriorating health or anticipated long waiting times. While treatment with DAAs pre-transplant may decrease the risk of delisting due to medical comorbidities, it may inadvertently increase waiting times and risk of death due to inability to use HCV+ donors. Using a unique dataset with information collected by a national dialysis provider as well as transplant outcomes and Medicare claims, we will determine whether kidney transplant is associated with a survival benefit compared to chronic dialysis in a diverse, national sample of wait-listed HCV+ patients. We will examine whether acceptance of HCV+ kidneys offers benefit versus waiting for a kidney transplant from an HCV-negative donor. Finally, we will compare time to transplant among wait-listed HCV+ patients who are treated versus untreated with DAAs. Given our ongoing access to dialysis provider data and the largest cohort of US HCV+ kidney transplant candidates ever assembled, the findings will motivate future research proposals and additional data linkages aimed at optimizing the care of HCV+ patients with end-stage renal disease.